Apparatus and method for virus detection

ABSTRACT

Embodiments of the present invention relate to a method comprising obtaining a radio frequency response of a lab-on-chip based resonator with virus deposited within a recess of the resonator, determining at least one parameter of the radio frequency response and identifying a type of the virus or a group to which the virus belongs based on the at least one parameter.

TECHNICAL FIELD

This invention relates to apparatus, systems and methods for virusdetection. In particular, but not exclusively, embodiments of thisinvention relate to uses of nanotechnology and radio frequencytechniques in identifying a type of virus.

BACKGROUND

It is widely known that many diseases are caused by viruses. It istherefore important to be able to detect viruses and identify a detectedvirus to be a particular type of virus as quickly as possible, since itcould enable diagnosis at the earliest stages of replication within thehost's system, and allow speedy medical decision-making. Moreover,accurate quantification of viruses is very essential for the developmentof their corresponding vaccines and it is desirable to be able todistinguish between different kinds of viruses presented in a sample.

Many studies are being conducted on developing sensing mechanisms thathelp speed up virus detection and identification. Most of the existingvirus screening and quantifying techniques suffer from limitations, suchas the need for extensive sample preparation and steps including viralisolation, extraction, and purification, or from the limitations thatthey are very costly and time consuming to carry out.

SUMMARY OF THE INVENTION

A first aspect of the present invention provides a method, comprising:obtaining a radio frequency response of a lab-on-chip based resonatorwith virus deposited within a recess of the resonator, determining atleast one parameter of the radio frequency response, and identifying atype of the virus or a group to which the virus belongs based on the atleast one parameter.

In one embodiment, said at least one parameter is an amplitude or achange of amplitude at a resonance frequency of the resonator with thevirus deposited therein.

In one embodiment, the method further comprises measuring said at leastone parameter of a radio frequency response when a different types ofvirus is deposited within the resonator, composing a lookup tablecontaining at least said two types of viruses and their respectivefrequency response measurements.

In one embodiment, the lab-on-chip based resonator comprises nanotubes,and said depositing virus within the recess of the resonator comprisesdepositing virus between the gaps of the nanotubes.

In one embodiment, the virus is mixed with functionalized nanoparticleswhen being deposited within a recess of the resonator.

In one embodiment, the nanoparticles are antibodies and/or quantum dots.

In one embodiment, the said obtaining a radio frequency response of theresonator is performed by a Vector Network Analyser (VNA), which isconfigured to collect a set of scattering parameter measurements todetermine the resonance frequency and a signal amplitude at theresonance frequency.

In one embodiment, said at least one parameter comprises at least oneof: a resonance frequency, a change in resonance frequency, a phase at aparticular frequency, and a phase shift at a particular frequency of thefrequency response.

In one embodiment, said obtaining a radio frequency response isperformed at a first temperature, and said determining determines saidat least one parameter of the radio frequency response obtained at thefirst temperature, wherein the method further comprises obtaining, at asecond temperature, a radio frequency response of the resonator with thevirus deposited within the recess of the resonator, determining a secondparameter of the radio frequency response obtained at the secondtemperature, and wherein said identifying a type of the virus or a groupto which the virus belongs is performed based on a comparison betweensaid first parameter and said second parameter.

In one embodiment, said the first temperature is 37° C., and the secondtemperature is 47° C.

In one embodiment, the method comprises identifying a type of the virusto be HIV if the first parameter and the second parameter aresubstantially identical, wherein the first parameter and the secondparameter are both a magnitude of the frequency response at theresonance frequency.

In one embodiment, said determining a signal amplitude at a resonantfrequency of the resonator at the first and the second temperatures isperformed by a Vector Network Analyser, which is configured to collect aset of scattering parameter measurements to determine the resonantfrequency and the signal amplitude.

A second aspect of the present invention provides an apparatus or asystem, comprising: a device for obtaining a radio frequency response ofa lab-on-chip based resonator with virus deposited within a recess ofthe resonator, a device for determining at least one parameter of theradio frequency response, at least one processor and at least onememory, causing the apparatus or the system to identify a type of thevirus or a group to which the virus belongs based on said at least oneparameter of the radio frequency response.

In one embodiment, said device for determining at least one parameter isconfigured to determine a magnitude or a change of magnitude at aresonance frequency of the resonator with the virus deposited therein.

In one embodiment, said device for obtaining a radio frequency responseof the resonator is a Vector Network Analyser (VNA).

In one embodiment, wherein said device for obtaining a radio frequencyresponse is configured to obtain a radio frequency response at both afirst temperature and a second temperature, and wherein said device fordetermining at least one parameter is configured to determine a firstparameter of the radio frequency response obtained at the firsttemperature and to determine a second parameter of the radio frequencyresponse obtained at the second temperature, wherein said at least oneprocessor and said at least one memory are configured to cause theapparatus or system to identify a type of the virus or a group to whichthe virus belongs based on a comparison between said first parameter andsaid second parameter.

In one embodiment, wherein the first temperature is 37° C., and thesecond temperature is 47° C.

In one embodiment, the apparatus or system comprises identifying a typeof the virus to be HIV if the first parameter and the second parameterare substantially identical.

In one embodiment, said at least one parameter comprises at least oneof: a resonance frequency, a change in resonance frequency, a phase at aparticular frequency, and a phase shift at a particular frequency of thefrequency response.

In one embodiment, said at least one processor and at least one memoryare configured to cause the apparatus to identify a type of the virus ora group to which the virus belongs based on said at least one parameterof the radio frequency response and data stored in the memory.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present invention will now be described by way ofexample with reference to the accompanying drawings:

FIG. 1 shows a cross-sectional view of a nano-tube based resonator usedin a first embodiment of the invention.

FIG. 2 shows a cross-sectional view of the nano-tube based resonatorused in the first embodiment of the invention with virus depositedtherein.

FIG. 3 shows functionalized nanoparticles (or quantum dots) and virussticking to them.

FIG. 4 shows a cross-sectional view of a resonator used in a secondembodiment of the invention.

FIG. 5 shows a cross-sectional view of the resonator used in the secondembodiment of the invention with virus deposited therein.

FIGS. 6a and 6b show a system for laboratory production of a virus of acertain amount.

FIGS. 7a, 7b and 7c show frequency responses of several types of virusesat 7° C., 37° C. and 47° C. respectively. FIG. 7d shows a comparison ofthe frequency responses of these viruses at these temperatures.

FIGS. 8a, 8b and 8c together illustrate effect of radio frequencysignals and temperature on virus.

FIG. 9 shows a method for compiling a lookup table according to someembodiments of the present invention.

FIG. 10 shows a method for determining a type of virus according to someembodiments of the present invention.

DETAILED DESCRIPTION

Embodiments of this invention provide a method for comprising: obtaininga radio frequency response of a lab-on-chip based resonator with virusdeposited within a recess of the resonator, determining at least oneparameter of the radio frequency response, and identifying a type of thevirus or a group to which the virus belongs based on the at least oneparameter.

FIG. 1 shows a nano-tube based resonator 102 implemented on alab-on-a-chip (LOC) used in a first embodiment of the invention. Alab-on-a-chip is a device that integrates one or several laboratoryfunctions on a single chip with a size in the order of millimeters to afew square centimeters. The lab-on-a-chip used for this embodimentcomprises a gap or indentation with small dimensions, e.g. in the rangeof several micros, on the lab-on-a-chip device and a mechanicalresonator comprising an array of vertical nanotubes placed within thegap.

In the embodiment shown in FIG. 1, the apparatus 102 comprises asubstrate 104, dielectric materials 106, input electrode metallization108, output electrode metallization 110 and nanotubes array 112.

The resonator 102 behaves as a band pass filter to RF signalspropagating through it and has a certain quality factor (Q factor). WhenRF signals propagate from input 108 to output 110, the resonator rejectsor attenuates RF signals with frequencies not matching its mechanicalresonance frequency. Therefore, most or all of these RF signals arereflected back and few of them at or very close to the resonancefrequency of resonator 102 are transmitted through the nanotubes array.At a RF signal frequency that matches the mechanical resonance of theresonator 102, a substantial proportion of power is transmitted throughalthough a small proportion of power is still reflected.

The nano-tubes array 112 may be isolated from the substrate by adielectric layer (not shown in the drawings) in case that the tubes aremetallic or made of semiconductor. The nano-tubes array 102 may befunctionalized so that it provides an enhanced stickiness to virus andcan more easily capture virus. The distances between the nano-tubes arelarge enough to host nanoparticles between them.

The mechanical resonance frequency of the nano-tubes array 112 andoverall frequency performance of the device 102 depends on a number ofdesign parameters: materials, diameter and length of the nano-tubes,distance between the nano-tubes and the properties of the dielectricmaterials that are used to decorate the array, and also the density ofthe nano-tubes in the array.

FIG. 2 illustrates the nano-tube based resonator 102 with virus specimenin a liquid form deposited among the nano-tubes. The liquid specimen maybe mixed with functionalized nano-particles or quantum dots, which couldbe magnetic, metallic or dielectric. FIG. 2 shows an arrangement readyfor measurements. As will be explained later, the deposition of virus onthe lab-on-chip device will change the frequency responsecharacteristics of the device.

FIG. 3 illustrates functionalized nano-particles (or quantum dots) 120and virions (virus particles) 122 sticking onto them. The functionalizednano-particles (or quantum dots) 120 are used to provide a carrier forthe virions 122 and to increase sensitivity of the measurements.

The virions 122 stick onto the nano-particles (or quantum dots) 120 moreeasily than directly onto nano-tubes. The nano-particles 120 may becoated with special materials to capture the virions 122 and make thevirus 122 stick to them.

FIG. 4 shows a cavity/gap coupling resonator 302 implemented on alab-on-a-chip device. The resonator 302 comprises a substrate 304,dielectric materials 306, input electrode metallization 308, outputelectrode metallization 310, a gap/cavity 314. The gap 314 behaves likea capacitance and the electrodes 308 and 310 behave like inductors to RFsignals. Thus the combination acts as an L-C resonance circuit to RFsignals and resonates at its resonance frequency.

The resonator 302 has a certain quality factor (Q factor) and behaveslike a band pass filter to RF signals propagating through it. When RFsignals propagate from input 308 to output 310, the resonator rejects orattenuates RF signals with frequencies not matching its mechanicalresonance frequency. Therefore, most or all of these RF signals arereflected back and few of them substantially at and near the resonancefrequency are transmitted through the resonator 302. At a frequency thatmatches the resonance frequency of the resonator 302, a substantialproportion of power is transmitted through although a small proportionof power is still reflected.

The resonance frequency and overall frequency performance of theresonator 302 depends on a number of parameters: dietetic material orother materials that are deposited above the substrate, distance betweenthe input and output, dimensions of the gap, etc.

FIG. 5 shows that virus specimen with nanoparticles (or quantum dots) isdeposited within the gap/cavity, and that the total arrangement is readyfor measurements.

The nanoparticles are dielectric materials and their insertion willchange the effective dielectric constant of the cavity, the air gapcapacitance and thus the resonant frequency and frequency responsecharacteristics as a consequence of changing the gap capacitance.

FIG. 6a illustrates a method for ensuring that equal amounts ofdifferent types of viral particles are used for radio frequencysignature analysis. It illustrates that four different retroviralparticles were produced employing the principle of genetic transcomplementation assay and was used for studying HIV, FIV, MPMV, and MMTVreplication. These trans complementation assays consist of a packagingconstruct, JA10 (MMTV), TR301 (MPMV), MB22 (FIV), and CMVΔR8.2 (HIV)expressing respective viral gag/pol genes, and therefore resulting inthe production of viral particles, which are capable of encapsulatingrespective retroviral RNAs. The source of the packageable RNA isprovided by DA024 (MMTV), SJ2 (MPMV) TR394 (FIV), and MB58 (HIV)transfer vectors. These transfer vectors express hygromycin resistanceas a marker gene, which monitors the successful retroviral particleproduction by quantitatively analyzing the transduced target cells withthis marker gene (FIG. 6a ). The number of Hygromycin-resistant(Hyg^(r)) colonies obtained should be directly proportional to theamount of viral particles produced and RNA that is packaged into thevirus (FIG. 6a ). An envelope expression plasmid (MD.G) based onvesicular stomatitis virus envelope G (VSV-G) was used to pseudotypedifferent retroviral particle. Briefly, in these assays, the threeplasmids (for example JA10+DA24+MD.G in the case of MMTV) wereco-transfected into 293T producer cells, which generated virus particlescontaining the encapsulated RNA (FIG. 6a ).

These virus particles were used to monitor the specific radio frequencysignatures for these retroviruses. In addition, these viral particleswere also used to infect target cells resulting in the transduction ofthese cells with the marker gene present on the packaged RNA, thusallowing for monitoring the propagation of the transfer vector RNA,which could only take place if the virus particles are efficientlyproduced. The rationale behind pseudotyping different retroviralparticles by a common VSV envelope glycoprotein (Env-gp) is based on thefact that all of these retroviral particles (HIV, FIV, MMTV, and MPMV)will be decorated by the similar Env-gp.

To ensure that equal amounts of viral particles are used for radiofrequency signature analysis, each transfection was carried out in thepresence of an independent DNA, pGL3 Control vector, expressing theluciferase gene. This allows monitoring the transfection efficiencies inour cell cultures as described previously. The amount of culturesupernatant (virus particle) used for radio frequency signature analysisfor each retrovirus was determined by following a normalization with thetransfection efficiencies using the relative light units/μg of protein(RLU).

In one embodiment, each kind of virus is suspended into Dulbecco'sModified Eagle Medium (DMEM), and each mixture is exposed to a radiofrequency signal with a power of 10 dBm and with a sweep from 10 MHz upto 13.6 GHz using the measurements setup which is shown in FIG. 6 b.

In the embodiment shown in FIG. 6b , a Vector Network Analyzer (VNA) isused to take the measurements. The VNA is able to take high frequencyscattering parameters measurements of a filled coaxial based resonatorstructure with appropriate medium at defined resonance frequency band tocharacterize viruses.

A virus specimen is loaded into a hosting RF coaxial resonatorstructure. The self-resonance frequency of the coaxial cables is set tobe above 30 GHz, and will not affect the measurements in theaforementioned frequency range, namely 10 MHz to 13.6 GHz. The system iscalibrated using SLOT transmission line techniques for the networkanalyzer to ensure that the measurements are representations of themixture solution, but not anything else. A typical calibration will movethe measurement reference planes to the end of the test cables.Therefore, it will exclude the effect of losses and phase shifts thatcould add noise to the measured signal.

FIG. 7 illustrates frequency response characteristics of four types ofviruses: FIV, MPMV, MMTV and HIV (corresponding to V1, V2, V3 and V4 inFIG. 7 respectively) at different temperatures. In the test, each kindof virus was suspended into Dulbecco's Modified Eagle Medium (DMEM)before deposited on the lab-on-chip device. A medium response(corresponding to M in FIG. 7), i.e. a response of the DMEM mediumdeposited on the lab-on-chip alone without any virus, is also measuredfor comparison with the responses for the viruses. For these four typesof viruses, an equal amount of viral particles have been used for theirradio frequency signature analysis.

As illustrated in FIGS. 7a, 7b and 7c , frequency response profiles ofthe viruses generally follow the medium frequency behavior, with anexpected deviation in magnitude at certain frequency bands, such as theresonance bandwidth. At this frequency band, the viruses are susceptibleto RF polarization which depends on the compositions of the virus itselfand its interaction with the medium polarity and/or ionic strength. Asthe viruses are of small sizes which are in the range of several tens ofnanometers (up to 300 nm) in diameter, the virions could be modeled asnanoparticles, and when they are subjected to propagation of RF fieldthey will get polarized due to the induced charging effect as in thecase of nanoparticles. This is because as the signal frequency increasesfrom a small level and signal wavelength becomes smaller. When the RFsignal wavelength becomes comparable with the size of virions, the RFsignal could modulate electrical charge distribution in the virus whichin turn can create a polarizing effect on the virions, cause the virusparticles to agitate and trigger impact ionization, which enablesdetection and identification of virus. The RF field propagating throughthe viruses will be altered in magnitude and phase depending on thevirus properties, such as dielectric constant and electrical resistivelosses. However, the extent of alteration to magnitude and phase isfrequency dependent and is different to signals at differentfrequencies. At the resonance frequency, the response exhibits a purelyresistive behavior. Thus, the viruses could change the frequencyresponse of the lab-on-chip under test, which in turn can be utilizedfor identification of virus type based on this amount of change.

FIG. 7a shows that the RF response at 7° C. of each type of virusfollows the medium response except at the resonance frequency around 12GHz, where the RF responses of the four types of viruses clearly differin their magnitudes. The response signal corresponding to the FIV (V1 inFIG. 7) is found to be close to the DMEM medium response behavior (M inFIG. 7) with reduction of magnitude of 0.3 dB at the resonancefrequency, while the signals corresponding to MPMV and MMTV (V2 and V3in FIG. 7 respectively) show a reduction of 2 and 2.4 dB, respectively.On the other hand, the HIV corresponding signal exhibits increment of0.75 dB at the resonance frequency.

FIGS. 7b and 7c shows the frequency responses of these four types ofviruses at 37° C. and 47° C. respectively. FIG. 7d shows a comparison ofsignal magnitudes at different temperatures for each of the four typesof viruses. It shows that when the temperature increases from 37° C. to47° C. the HIV associated signals do not change with the increase intemperature. However the other three types of viruses all have a morenoticeable change in their signal magnitudes. Thus this approach can beused to detect a number of types of viruses without the need forlabeling or biomarker. This also could provide a roadmap for theidentification of viruses as well as molecular target candidates ofother biological types.

Initially at 7° C. and as has been discussed, some virions exhibitnegative differential DC resistance (MMTV, MPMV and FIV) and otherexhibits positive differential DC resistance (HIV). As temperatureincreases, the liquid sample containing virus becomes less conductive,because the thermal vibrations in the lattice increase which causes moreelectron scattering and more collisions between electrons take place,slowing down flow of electrons. Consequently the rate of electric energytransfer by heating increases along with the electrical resistancecausing the magnitude of the S₁₁ parameter in the S-parameters measuredby the VNA to shift up.

In one embodiment, the frequency responses can be used to classifyviruses. Viruses are classified based on their morphology, capsid andnucleic acid. Both MMTV and MPMV are categorized as beta retrovirusesand this explains their close frequency behaviors. Similarly, FIV andHIV belong to the lentivirus group, and their frequency responses areclose to each other. The capsid surrounds the virus and it is composedof a finite number of proteins. The lipid bilayer has an averagethickness of about 5 nm, with a typical dielectric constant of 2. Thechange in S₁₁ parameter (one of the S parameters measured by the VNA)level is due to the associated intrinsic DC differential resistance ofthe virus itself. The increment in S₁₁ parameter is interpreted as theHIV virus introducing losses which are added to the mixture, thusincreasing the effective total DC resistance, causing the level to beshifted up by 0.75 dB. Hence the virus is considered as a lossy materialthat exhibits certain loss dispersion over frequency. On the other side,the decrement in S₁₁ parameter can be attributed to viruses (MMTV andMPMV) exhibiting negative DC resistance. This will in turn reduce thetotal effective resistance of the mixture by subtracting the DMEM mediumlosses, thus causing the level to be shifted downward. Such a strategystreamlined the interpretation of the results in terms of specific radiofrequency signatures for these different types of viruses, which couldthen be attributed solely to the specific nature of respective viralparticles not due to the presence of different Env-gp.

As will be understood by a person of ordinary skill, profiles similar tothose in FIG. 7 can be drawn up for phase shifts made to RF signalspassing through the lab-on-chip device with virus deposited therein inthe aforementioned frequency range (10 MHz to 13.6 GHz). The phase shiftcharacteristics can also be used to identify a type of virus.

FIG. 8 illustrates the temperature effect on the viruses. FIG. 8a showsthe viral particles distribution within the medium when there is noapplied RF field. As depicted in FIG. 8b , with RF propagating throughthe particles, the particles get polarized and align at the deviceelectrodes based on their polarity—negative particles are attracted tothe positive electrode, and the positive particles are attracted to thenegative electrodes. The virus particles initially possess highconductivity. However, with an increased temperature, their morphologychanges and they become more agitated and electrically more resistive asshown in FIG. 8c . Since different viral particles were producedfollowing the DNA transfection into 293T cells, which allowed them tohave a common lipid bilayer in addition to being pesudotyped by a commonEnv-gp as explained earlier. Therefore, the polarization of these viralparticles at different temperatures can consequently be attributedspecifically to each viral particle used for the study.

The above demonstrates the use of high frequency measurements atdifferent temperatures for detection of retroviruses and lentiviruses insuspended DMEM based solutions. Among the label-free methods that may beused to directly detect viruses, the method according to embodiments ofthe present invention provides a combination of advantages, such as highsensitivity, quick response, low cost, high throughput, and ease of use.

FIG. 9 illustrates a method for obtaining a lookup table, which can beused to identify several types of viruses according to an embodiment ofthe present invention.

In step 901, a virus medium, such as DMEM, is deposited on a lab-on-chipdevice, such as a device shown in FIG. 1 or 4. In step 902, a RFresponse of the lab-on-chip device with the medium deposited therein isobtained at a first temperature, e.g. 37° C., using a Vector NetworkAnalyzer. The measurements of the response, including a magnitude of theRF response at a resonance frequency of the device are recorded.

In step 903, a type of virus is mixed with the virus medium and themixture is deposited within the lab-on-chip device. In step 904, a RFresponse is obtained for the lab-on-chip device with the mixturedeposited therein at the same temperature, namely 37° C. in thisembodiment. Measured parameters of the RF response, including amagnitude of the RF response at the resonance frequency, are recorded.

In step 905, steps 903 and 904 are repeated for different types ofviruses at the first temperature, namely 37° C. in this embodiment. Anequal amount of virus is used for the frequency response analysis forthe different types of viruses.

In step 906, a lookup table is compiled. The table comprises thedifferent types of viruses and their corresponding frequency responseproperties, including magnitudes (and/or changes in signal magnitudescompared to the medium response) at their resonance frequencies at thefirst temperature (37° C. in this embodiment). The following shows anexample of a format of the lookup table.

TABLE 1 5) Change in 4) Magnitude of magnitude at the frequency responseresonance frequency at the resonance compared to the Virus 1) Dielectric3) Resonance frequency medium response type constant 2) Phase frequency(at 37° C.) (at 37° C.) HIV FIV MMTV MPMV

In an optional step 907, steps 901-906 are repeated at a secondtemperature, e.g. 47° C. For each type of virus, the difference ofsignal magnitudes at the resonance frequency at the first and the secondtemperatures are calculated and recorded the change in the lookup table.

FIG. 10 illustrates a process of identifying a virus to be a particulartype of virus according to one embodiment of the present invention.

In step 1001, a specimen, such as a blood sample, is obtained. This maybe obtained from a patient. In step 1002, a virus medium, e.g. DMEM orother functionalized nanoparticles, is added to the specimen. The virusmedium helps increase sensitivity of the measurements and helpsattaching the viral particles to the nanoparticles.

In step 1003, the modified specimen is deposited on a resonator, such asthe lab-on-chip device illustrated in FIG. 1 or 4. In step 1004, a RFfrequency response is measured using, e.g. a Vector Network Analyser, atthe first temperature.

In step 1005, the measurement results are used to determine RF frequencyresponse parameters, such as a frequency shift and magnitude at theresonance frequency. In step 1006, a virus type is determined bychecking at least one of the determined parameters against data in apre-defined lookup table, e.g. a table obtained in step 906. Forexample, a magnitude at the resonance frequency of the device with virusdeposited therein can be checked against the data in column 4 of table1, and a type of virus can be determined if the magnitude corresponds tothe data of any one of HIV, FIV, MMTV and MPMV in column 4 of table 1.This determination may be performed manually or automatically by acomputer software program run on a computer.

Step 1007 can be used as an alternative way of identifying a type ofvirus or an additional step to confirm the virus type determined in step1006. In step 1007, steps 1004 and 1005 are repeated at a secondtemperature, e.g. 47° C. The change in signal magnitude at the resonancefrequency when the temperature is changed from the first temperature tothe second temperature is determined. By checking the change ofmagnitude at the resonance frequency against data in a pre-definedlook-up table, e.g. data in column 4 and/or column 5 of table 1 obtainedin step 907, it can be determined whether the virus is HIV, FIV, MMTV orMPMV. This determination may be performed manually or automatically by acomputer software program run on a computer.

Methods according to various embodiments of the present invention may beperformed by using a Vector Network Analyzer to measure parameters ofthe frequency responses of a lab-on-chip based resonator with virusdeposited within. As set out above, a user may manually check themeasured parameters against a pre-defined look-up table compiledaccording to method illustrated in FIG. 9. Alternatively, data of thelook-up table may be stored in a memory, and a processor may be used tocheck the measured parameters of the frequency response against thestored data of the look-up table. The processor and the memory may beprovided in a separate device, which operatively connects to the VNA.Alternatively, the VNA, the processor, and the memory may be integratedinto a single device, which may be a portable device.

The advantages of adopting the RF technology and nano-technologies invirus detection include avoiding the use of biomarker and utilize thechange in the frequency response caused by the present of the virusinside a sample, such as human blood. The RF detection based methodologyaccording to various embodiments of the present invention providefollowing: 1) quick and fast initial screening: the time for determiningthe presence of virus being less than 1 minute; 2) the possibility ofcharacterizing virus using a living cell rather than the conventionalway of using dead cell; 3) quick identification of a type of virus afterthe initial screening by processing the RF response, extracting certainparameters and comparing with a Lookup table for virus properties using.e.g. a computer based software program; 4) Suitability for Emergencycases: fast and quick check; 5) compact size; and 6) ability to detect avariety of virus.

The present invention is not to be limited in scope by the specificaspects and embodiments described herein. Indeed, various modificationsof the invention in addition to those described herein will becomeapparent to those skilled in the art from the foregoing description andaccompanying figures. Such modifications are intended to fall within thescope of the appended claims. Moreover, all aspects and embodimentsdescribed herein are considered to be broadly applicable and combinablewith any and all other consistent aspects and embodiments, asappropriate.

The invention claimed is:
 1. A method comprising: obtaining at a firsttemperature a radio frequency response of a lab-on-chip based resonatorwith a virus deposited within a recess of the resonator, determining atthe first temperature a first value of at least one parameter of theradio frequency response, obtaining, at a second temperature, a radiofrequency response of the resonator with the virus deposited within theresonator; determining at the second temperature a second value of theat least one parameter; and identifying a type of the virus or a groupto which the virus belongs based on a comparison between the first valueand the second value, wherein the first temperature is 37° C., and thesecond temperature is 47° C.
 2. The method of claim 1, wherein the atleast one parameter comprises an amplitude or a change of amplitude at aresonance frequency of the resonator with the virus deposited therein.3. The method of claim 2, wherein determining the amplitude at theresonance frequency of the resonator at the first and the secondtemperatures is performed by a Vector Network Analyser.
 4. The method ofclaim 1, further comprising: measuring at the first temperature thefirst value of the at least one parameter when a different types ofvirus is deposited within the resonator, compiling a lookup tablecontaining at least the measured first value obtained for the virus andthe different type of virus.
 5. The method of claim 1, wherein thelab-on-chip based resonator comprises nanotubes, and the virus isdeposited between gaps of the nanotubes.
 6. The method of claim 1,wherein the virus is mixed with functionalized nanoparticles when beingdeposited.
 7. The method of claim 6, wherein the functionalizednanoparticles are antibodies and/or quantum dots.
 8. The method of claim1, wherein obtaining a radio frequency response of the resonator isperformed by a Vector Network Analyser (VNA).
 9. The method of claim 1,wherein the at least one parameter comprises at least one of: aresonance frequency, a change in resonance frequency, a phase at aparticular frequency, and a phase shift at a particular frequency of thefrequency response.
 10. The method of claim 1, wherein the virusidentified is HIV if the first value and the second value aresubstantially identical, wherein the at least one parameter is amagnitude of the frequency response at the resonance frequency.
 11. Anapparatus comprising: a device configured to obtain, at a firsttemperature and a second temperature, a radio frequency response of alab-on-chip based resonator with a virus deposited within a recess ofthe resonator, a device configured to determine a first value of atleast one parameter of the radio frequency response obtained at thefirst temperature and to determine a second value of the at least oneparameter of the radio frequency response obtained at the secondtemperature, at least one processor and at least one memory for storingthe first and second value, the processor causing the apparatus toidentify a type of the virus or a group to which the virus belongs basedon a comparison between the first and second values of the at least oneparameter, wherein the first temperature is 37° C., and the secondtemperature is 47° C.
 12. The apparatus of claim 11, wherein the atleast one parameter is a magnitude or a change of magnitude at aresonance frequency of the resonator with the virus deposited therein.13. The apparatus of claim 11, wherein the device for obtaining theradio frequency response of the resonator is a Vector Network Analyser(VNA).
 14. The apparatus of claim 11, wherein the first value and thesecond value are substantially identical and the virus is identified tobe HIV.
 15. The apparatus of claim 11, wherein the at least oneparameter comprises at least one of: a resonance frequency, a change inresonance frequency, a phase at a particular frequency, and a phaseshift at a particular frequency of the frequency response.
 16. Theapparatus of claim 11, wherein the at least one processor and the atleast one memory are configured to cause the apparatus to identify thetype of the virus or the group to which the virus belongs based on thefirst and second values of the at least one parameter and data stored inthe memory.